Objectives To investigate leukocyte patterns and measures of serotonergic dysfunction in the intrathecal compartment. It has been reported that normal serotonergic synthesis and metabolism are disrupted by HIV and SIV infection leading to an excessive production of quinolinic acid. Our study was designed to replicate and extend these observations in the SAIDS model. Levels of quinolinic acid were elevated in the cerebrospinal fluid of SIV-infected rhesus monkeys and were generally correlated with disease progression. In addition, increasing quinolinic levels were also associated with changes in the numbers of CD4+ and CD8+ lymphocytes in the CSF. Neither quinolinic acid levels or lymphocyte numbers were altered by a viral variant, SHIV, which did not cause clinical illness. These data support the use of quinolinic acid as a measure of disease progression, although it remains to be established whether it is a causative mechanism of CNS pathology, or an indirect correlate of systemic illness. Key words SAIDS, SIV, quinolinic acid, cerebrospinal fluid, lymphocyte subsets